Lecture 6 - B cell Activation Flashcards
Changes in B cells after activation by antigen
- Antibody secretion
- Somatic mutation - additional diversity
- Isotype switching
_________ is the process responsible for changing membrane IgM to secreted IgM
Alternative RNA processing
Transmembrane IgM is expressed by ________, while secreted IgM is expresed by ___________
Transmembrane = Unactivated B cell
Secreted = Activated B cell (differentiated into a plasma cell)
In somatic hypermutation what do the red bars indicate? Where are they most common?
Nucleotide substitutions
Typically occur in the hypervariable regions (CDR) of the V domain
The CDR regions of the heavy and light chains make up the…
antigen binding site
Somatic hypermutation is mediated by…
activation-induced cytidine deaminase
(C–>U)
The light chain V region is made of _____ DNA segments and ______ DNA segments
Framework (FR)
Hypervariable (HV)
Isotype switching results in
Ig molecules with different C regions but identical antigen specificity
Isotype switching is mediated by
AID
activation induced cytosine deaminase
AID selectively targets the ______ regions during isotype switching
Sµ and S γ1 switch regions
There is no switch region between…
Why?
Cµ + Cδ
Because the B cell can express both via alternative splicing
What happens after AID nicks the DNA in the switch regions during isotype switching?
The DNA inbetween the switch regions is looped out, and the immunoglobulin gene is made into a functional molecule (IgG1, in the figure given)
This molecule is turned on upon B cell activation
Activation-induced cytosine deaminase
AID
A particular isotype switching is determined by…
TH cell cytokines
Effector functions of antibodies
Neutralization
Opsonization
Complement activation
Antibody mediated opsonization involves…
IG binds to bacteria, and the Fc region binds to the FcR on Macrophage to facilitate phagocytosis
Complement activation by antibodies leads to…
- opsonization
- Cell death via proteolytic enzymes
- Inflammation
IgM conformational structure
What different thing does it contain?
Monomer = membrane, Pentamer = secretion
Contains a stabilizer protein /J-chain in the middle of its pentamer (NOT the J chain from VDJ recombination)
IgM binding properties
Low affinity
but high avidity due to its 10 binding sites
Functions of IgM (3)
- 1st secreted during immune response
- Activates complement (& agglutination)
- Transported into mucosal secretions
IgM doesn’t need….
Coomb’s reagent to crosslink
IgM is present on the membrane of…
naive B cells
Highest Ig (concentration) in serum is ____
IgG
what are the subclasses of IgG, and what function do they differ in?
IgG1-4
they activate complement at different rates (3>1>2)
*IgG4 does not activate complement
IgG molecules bind to __ receptors…on which cells?
Fc-gamma receptors
on neutrophils, MQ, and NK cells
IgG differ in the structure of…
the hinge region
IgG3 has the most flexibility but is most susceptible to proteolytic cleavage (effectively lowering its half-life)
IgG4 is functionally…
monovalent
can dissociate and recombine to a bivalent molecule (binds two epitopes)
Bivalent IgG4 has a ___ avidity than monovalent.
Why?
Lower avidity
because it can only bind one of each type of antigen instead of two (monovalent has two CDR regions that have the same specificity)
IgA subclasses and structures
IgA1 = Monomer (mostly)
IgA2 = Dimer
Secretory IgA is usually a dimer
IgA dimer is connected via
a J chain (different from VDJ)
IgA function
Neurtralization of microorganisms
NOT an effected complement inducer
Strep pneumo, H. influenzae, and Mengingococcus all produce ____ that gives them tissue access
IgA proteases
IgE structurally contains…
an extra CH domain
NO hinge region
IgE is usually in LOW concentrations, but is present in higher amounts in people with…
allergies and helminth infections
IgE binds to ___ on what cells?
FcE receptors
on mast cells and basophils
induces degranulation
IgD is present with _____ on what cells?
with IgM
on naive mature B cells
Highest serum immunoglobulin
IgG1
Lowest serum Ig isotype
IgD
IgD secreting plasma cells are located where?
URT
___ is pretty much the only isotype to be transported across epithelium
IgA
Isotypes:
M, G1, G3 are more for…
G1,2,3,4 + A are more for
M, G1, G3 = Complement
G1,2,3,4 + A = Neutralization
What are the two reversible and regulated steps in B cell life cycle
- Activation of coexpression of IgM and IgD on surface
- Antibody synthesis changes from membrane Ig to secreted
The five irreversible steps in B cell life cycle
- V region assembly
- Junctional diversity (imprecise joining & P/N NT insertion)
- Assembly of transcriptional machinery (promoter and enhancer brought together)
- Somatic hypermutation
- Isotype switching
